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Protein

Proteinase-activated receptor 4

Gene

F2RL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.1 Publication

GO - Molecular functioni

  • G-protein coupled receptor activity Source: Reactome
  • thrombin-activated receptor activity Source: ProtInc

GO - Biological processi

  • blood coagulation Source: ProtInc
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: ProtInc
  • platelet activation Source: Reactome
  • platelet dense granule organization Source: BHF-UCL
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: GO_Central
  • positive regulation of release of sequestered calcium ion into cytosol Source: BHF-UCL
  • positive regulation of Rho protein signal transduction Source: GO_Central
  • response to wounding Source: ProtInc
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Blood coagulation, Hemostasis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127533-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
R-HSA-456926. Thrombin signalling through proteinase activated receptors (PARs).
SIGNORiQ96RI0.

Names & Taxonomyi

Protein namesi
Recommended name:
Proteinase-activated receptor 4
Short name:
PAR-4
Alternative name(s):
Coagulation factor II receptor-like 3
Thrombin receptor-like 3
Gene namesi
Name:F2RL3
Synonyms:PAR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:3540. F2RL3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini48 – 82ExtracellularSequence analysisAdd BLAST35
Transmembranei83 – 103Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini104 – 108CytoplasmicSequence analysis5
Transmembranei109 – 129Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini130 – 151ExtracellularSequence analysisAdd BLAST22
Transmembranei152 – 172Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini173 – 192CytoplasmicSequence analysisAdd BLAST20
Transmembranei193 – 213Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini214 – 247ExtracellularSequence analysisAdd BLAST34
Transmembranei248 – 268Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini269 – 283CytoplasmicSequence analysisAdd BLAST15
Transmembranei284 – 304Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini305 – 319ExtracellularSequence analysisAdd BLAST15
Transmembranei320 – 343Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini344 – 385CytoplasmicSequence analysisAdd BLAST42

GO - Cellular componenti

  • extracellular region Source: Reactome
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47R → A: No proteolytic cleavage (by thrombin or trypsin). 1 Publication1
Mutagenesisi68R → A: No effect on receptor activation. 1 Publication1

Organism-specific databases

DisGeNETi9002.
OpenTargetsiENSG00000127533.
PharmGKBiPA27949.

Chemistry databases

ChEMBLiCHEMBL4691.

Polymorphism and mutation databases

BioMutaiF2RL3.
DMDMi116242700.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
PropeptideiPRO_000001276218 – 47Removed for receptor activationBy similarityAdd BLAST30
ChainiPRO_000001276348 – 385Proteinase-activated receptor 4Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi149 ↔ 228PROSITE-ProRule annotation

Post-translational modificationi

A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei47 – 48Cleavage; by thrombin or trypsinBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ96RI0.
PeptideAtlasiQ96RI0.
PRIDEiQ96RI0.

PTM databases

iPTMnetiQ96RI0.
PhosphoSitePlusiQ96RI0.

Miscellaneous databases

PMAP-CutDBQ96RI0.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.

Gene expression databases

BgeeiENSG00000127533.
CleanExiHS_F2RL3.
ExpressionAtlasiQ96RI0. baseline and differential.

Interactioni

Protein-protein interaction databases

BioGridi114481. 1 interactor.
STRINGi9606.ENSP00000248076.

Chemistry databases

BindingDBiQ96RI0.

Structurei

Secondary structure

1385
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 46Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZPKX-ray1.80P/Q46-53[»]
3QDZX-ray2.80E/F39-47[»]
ProteinModelPortaliQ96RI0.
SMRiQ96RI0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96RI0.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi301 – 305Poly-Leu5

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFSN. Eukaryota.
ENOG410YD35. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG096365.
InParanoidiQ96RI0.
KOiK04236.
OMAiCHDALPL.
OrthoDBiEOG091G0C2F.
PhylomeDBiQ96RI0.
TreeFamiTF350010.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003944. Prot_act_rcpt_4.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01430. PROTEASEAR4.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96RI0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWGRLLLWPL VLGFSLSGGT QTPSVYDESG STGGGDDSTP SILPAPRGYP
60 70 80 90 100
GQVCANDSDT LELPDSSRAL LLGWVPTRLV PALYGLVLVV GLPANGLALW
110 120 130 140 150
VLATQAPRLP STMLLMNLAA ADLLLALALP PRIAYHLRGQ RWPFGEAACR
160 170 180 190 200
LATAALYGHM YGSVLLLAAV SLDRYLALVH PLRARALRGR RLALGLCMAA
210 220 230 240 250
WLMAAALALP LTLQRQTFRL ARSDRVLCHD ALPLDAQASH WQPAFTCLAL
260 270 280 290 300
LGCFLPLLAM LLCYGATLHT LAASGRRYGH ALRLTAVVLA SAVAFFVPSN
310 320 330 340 350
LLLLLHYSDP SPSAWGNLYG AYVPSLALST LNSCVDPFIY YYVSAEFRDK
360 370 380
VRAGLFQRSP GDTVASKASA EGGSRGMGTH SSLLQ
Length:385
Mass (Da):41,133
Last modified:October 17, 2006 - v3
Checksum:iFACE32F10D5C561E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028300120A → T.3 PublicationsCorresponds to variant rs773902dbSNPEnsembl.1
Natural variantiVAR_028301215R → Q.Corresponds to variant rs2230799dbSNPEnsembl.1
Natural variantiVAR_012852296F → V.1 PublicationCorresponds to variant rs2227346dbSNPEnsembl.1
Natural variantiVAR_012853310P → L.1 PublicationCorresponds to variant rs2227376dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF080214 mRNA. Translation: AAC28860.1.
AF055917 mRNA. Translation: AAC25699.1.
AY431102 mRNA. Translation: AAR08487.1.
AF384819 Genomic DNA. Translation: AAK61908.1.
BC074782 mRNA. Translation: AAH74782.2.
CCDSiCCDS12350.1.
RefSeqiNP_003941.2. NM_003950.3.
UniGeneiHs.137574.

Genome annotation databases

EnsembliENST00000248076; ENSP00000248076; ENSG00000127533.
GeneIDi9002.
KEGGihsa:9002.
UCSCiuc002nfa.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF080214 mRNA. Translation: AAC28860.1.
AF055917 mRNA. Translation: AAC25699.1.
AY431102 mRNA. Translation: AAR08487.1.
AF384819 Genomic DNA. Translation: AAK61908.1.
BC074782 mRNA. Translation: AAH74782.2.
CCDSiCCDS12350.1.
RefSeqiNP_003941.2. NM_003950.3.
UniGeneiHs.137574.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZPKX-ray1.80P/Q46-53[»]
3QDZX-ray2.80E/F39-47[»]
ProteinModelPortaliQ96RI0.
SMRiQ96RI0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114481. 1 interactor.
STRINGi9606.ENSP00000248076.

Chemistry databases

BindingDBiQ96RI0.
ChEMBLiCHEMBL4691.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ96RI0.
PhosphoSitePlusiQ96RI0.

Polymorphism and mutation databases

BioMutaiF2RL3.
DMDMi116242700.

Proteomic databases

PaxDbiQ96RI0.
PeptideAtlasiQ96RI0.
PRIDEiQ96RI0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248076; ENSP00000248076; ENSG00000127533.
GeneIDi9002.
KEGGihsa:9002.
UCSCiuc002nfa.4. human.

Organism-specific databases

CTDi9002.
DisGeNETi9002.
GeneCardsiF2RL3.
HGNCiHGNC:3540. F2RL3.
MIMi602779. gene.
neXtProtiNX_Q96RI0.
OpenTargetsiENSG00000127533.
PharmGKBiPA27949.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFSN. Eukaryota.
ENOG410YD35. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG096365.
InParanoidiQ96RI0.
KOiK04236.
OMAiCHDALPL.
OrthoDBiEOG091G0C2F.
PhylomeDBiQ96RI0.
TreeFamiTF350010.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127533-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
R-HSA-456926. Thrombin signalling through proteinase activated receptors (PARs).
SIGNORiQ96RI0.

Miscellaneous databases

EvolutionaryTraceiQ96RI0.
GeneWikiiF2RL3.
GenomeRNAii9002.
PMAP-CutDBQ96RI0.
PROiQ96RI0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127533.
CleanExiHS_F2RL3.
ExpressionAtlasiQ96RI0. baseline and differential.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003944. Prot_act_rcpt_4.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01430. PROTEASEAR4.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAR4_HUMAN
AccessioniPrimary (citable) accession number: Q96RI0
Secondary accession number(s): O76067, Q6DK42
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.